Process for the manufacture of pyridine-3-carboxylic acid amides



Patented Feb. 15, 1927.

UNITED STATES.

PATENT-OFFICE;

m HARTMANN SEIBERTH, OF BASEL, SWITZERLAND, ASSIGNOBS TO THE ITEM SOCIETY OF CHEMICAL INDUSTRY IN BASLE, OF BASEL, SWITZERLAND.

rnoonss non rim murncrunn or rxnr mn-a-cmnoxnrc Aoro .Am'nns.

No Drawing: Application filed December 11; 1925, Serial Rim-74,891, and in Switzerland December 20,

In Patent 1,403,117 there is described a process for the manufacture of dialkylamides of nicotinic acid (pyridine-3-carboxylic acid) consisting in heating a halide of nicotinicacid with a salt. of a dialkylamide for several hours at a temperature of 160- 180 C. 1

By the present invention p ridine-3-carboxylic acid amides, substitute in the amide group, may be obtained by causing a quinol inic acid anhydrlde to react with an amine, preferably of the formula Instead of diethylamine another saturated or unsaturated secondar amine may be used, for instance dipropy amine, diamylamine, methylpropylamine, ethylpropylamine, diallylamine or piperidine.

The following example illustrates the invention.

1 part by weight of quinolinic acid anhydride is intro uced into 3 parts'of diethylamine. The mixture is boiledfor 2 .hours in a reflux apparatus and the excess of diethylamine is distilled. The residue is heated to 180 C. Carbon dioxide and diethylamine are evolved. When no. more carbon dioxide is evolved'tlie oily residue is distilled under diminished pressure, whereby the pyridine-3-carboxylic acid diethylamide described in Patent No. 1,403,117'

passes over as a bright oil.

By substituting for the diethylamine in the foregoing example dipropylamine, diamylamine or piperidine, there is obtained respective] pyridine-3-carboxylic acid dipropylami e, pyridine-3-carboxylic acid diamylamide or pyridine-3-carboxylic acid oo-moluba N cooH-Nmomn aralkyl, and coiivertin the product of the reaction thus obtained, yheating it, into the corresponding pyridine-3-carboxylic .acid

amide. This latter is obtained in pure form by distillation, preferably-under diminished pressure. v

"For example, when quinolinic acid anhyvdride is caused to react withdiethylamine there is first produced the diethylamine salt of qumolinic diethylamic acid. This decomposes when heated into pyridine-3-carboxylic acid diethylamide, carbon dioxide and diethylamine. When elimination of carbon dioxlde is finished the pyridine-3-carboxylic acid diethylaniide may be distilled, preferably under diminished pressure.

The following formulae may be" presumed to represent the reaction comcmoi-scoiwmclm),

lee:

i CHz-CH CON on CHrCHI r1 which are described in U. S. Patent No. 1,403,117 and in the Swiss Patent 91,104,.respectively.

In the same manner N-disubstituted ampiperidide, corresponding with the formuides of nicotinic acid havingunsaturated or mixed alkyl, or further aryl, or mixed arylalkyl residues are obtained, for instance- N icotinic acid diallylamide, corresponding With the formula:

CON CHr-CH=CHa CHg-CH=CHI which is an oil soluble in water and boiling at 147 C. under 3 mm. pressure.

Nicotinic acid methylpropylamide, corresponding with the formula:

OHa

CHICHaCHt which is a yellowish oil easily soluble in water and boiling at 174 C. under 16 mm.

pressure.

Nicotinic acid ethylpropylamide, WhlCll 1s also an oil soluble in water and boiling at 173 C. under 15 mm. pressure.

Nicotinic acid diphenylamlde, corresponding with the formula:

WW2: KN/

which forms colourless crystals, melting at 150, and is easily soluble in dilute hydrochloric acid, somewhat soluble in boiling water', diflicultly soluble in ether and benzene.

Nicotinic acid phenylethylamlde, corresponding with the formula:

CHrCHrC|H CON ' Hg-CHz-CaHl which forms a viscous oil, boiling at 27 0 C.

under 7 mm. pressure, and is soluble in dilute hydrochloric acid, alcohol, ether and benzene, somewhat soluble in boiling water.

What we claim is A process for the manufacture of pyriformula a HN where R and R, represent a monovalent hydrocarbon radical, and then heating to eliminate carbon dioxide from the product of the reaction. u

3. A process for the manufacture of -N- dialkylamides of pyridine-3-carboxylic acid, by causing a quinolinic acid anhydride to react with a secondary amine of the formula acid anhydride to react with a secondary amine, then heating to eliminate carbon dioxide from the product of the reaction and distilling the amide of pyridine-3-carboxylic acid thus formed.

5. A process for the manu acture of p ridine-3 carboxylic acid amides substitute in the amide group, by causing a quinolinic' acid anhydride to react with an amine of the formula I a HN where R and R, represent a monovalent hydrocarbon radical, then heating to eliminate carbon dioxide from the product of the reaction and distilling the amide of pyridine-3-carbox'ylic acid thus formed.

6. A process for the manufacture of N dialkylamides of pyridine-3-carboxylic acid, by causing a quinolinic acid anhydride to react with a secondary amine of the formula where R and R represent alkyl groups, then heating to eliminate carbon dioxide from the product of the reaction and distilling the N- dialkylamide of pyridine-3-carboxylic acid thus formed.

7. A process for the manufacture of pyridine-3-carboxylic acid dietliylamide, by causing quinolinic acid anhydride to react with diethylaminc, and heating to eliminate carbon dioxide from the product of reaction.

8. A process for the manufacture of pyri- Ddine-Zi-carboxylic acid diethylamide, by causing quinoliuic acid anhydride to react with diethylan'iine, heating to eluiinate carbon dioxide from the product of the reaction, and distilling the N-diethylamide of pyridine-3- carboxylic acid.

9. A process for the manufacture of pyr'i- I dine-3-carboxylic acid diethylamide, by causing quinolinic acid anhydride to react with dicthylamine, heating to eliminate carbon dioxide from the product of the reaction, and distilling the N-diethylamide of pyridine-3-carboxylic acid under diminished pressure.

In witness whereof We have hereunto signed our names, this 30th day of Novem' ber, 1925.

MAX HARTMANN. MAX SEIBERTH. 

